Neurodevelopmental outcomes in infants exposed in utero to antipsychotics: a systematic review of published data

Abstract

The proportion of pregnancies exposed to either second-generation antipsychotics (SGAs) or first-generation antipsychotics (FGAs) varies between 0.3%-2% of all pregnancies, but, until now, little is known about the potential neurobehavioral teratogenicity of antipsychotics. Assessing this safety facet is the aim of this article. PubMed, Scopus, and Google Scholar were searched for eligible articles. PubMed (1954 to May 2016) was searched using several medical subject headings, variously combined. PubMed search results were also limited using the search filter for human studies published in English. Scopus and Google Scholar searches were filtered for article title (antipsychotics/neuroleptics, pregnancy). After excluding duplicates, 9,250 articles were identified and 29 met the following inclusion criteria: only articles that provided original/primary data on neurodevelopmental outcome in human offspring older than 4 months of age, independently of the study design, were selected for review. Indeed, some relevant neurodevelopmental milestones are achieved at this time. Length of study and neurodevelopmental assessment methodology did not influence the study selection. Unfortunately, published data on neurodevelopmental teratogenicity of SGAs mainly derive from case reports and small case-series studies. Even findings emerging from case-control and prospective/retrospective studies are of limited clinical relevance because of their small sample sizes. Limited data are also available on FGAs. Hence, we have to conclude that the long-term neurodevelopmental outcomes for children exposed in utero remain unclear. Low to very low quality evidence of retrieved data makes impossible to confirm or exclude potential long-lasting untoward effects on infant neurocognitive development associate with antenatal exposure to either SGAs or FGAs.

Antipsychotic use in pregnancy and risk of attention/deficit-hyperactivity disorder and autism spectrum disorder: a Nordic cohort study

“…6 The risks of congenital anomalies and short-term neonatal complications associated with antipsychotic exposure in utero have been evaluated in epidemiologic studies, [7][8][9] however, data on the risk of neurodevelopmental disorders during childhood are sparse. [10][11][12][13] This is despite potential neurotoxic effects of some antipsychotics in vitro and in vivo, 14 and evidence that these substances cross the placenta. 15 Two recent systematic reviews 11 12 concluded that there was no clear evidence of longterm effects after exposure to antipsychotics in utero.…”

Head circumference in infants with nonopiate-induced neonatal abstinence syndrome

“…The effects of antidepressants and antipsychotics on infant development are yet to be reported. 18,19 For these reasons, continuous measurement of HC and developmental assessments are important in nonopioid NAS infants to reveal any associations. Further follow-up studies are needed since follow-up data were not obtained in this study.…”

Antidepressants, Antipsychotics, and Mood Stabilizers in Pregnancy: What Do We Know and How Should We Treat Pregnant Women with Depression

“…There was no difference between the two groups for cognitive, language, motor, social, and emotional at 2, 6, and 12 months of age (Shao et al, 2015). Gentile and Fusco (2017) searched the English literature for neurodevelopmental studies in children exposed in utero to second generation antipsychotic drugs between1954 and 2016, and found mainly case reports and small case series. They performed a meta-analysis, on long-term outcomes of 35 healthy infants exposed in utero to antipsychotics.…”

“…They performed a meta‐analysis, on long‐term outcomes of 35 healthy infants exposed in utero to antipsychotics. Of these cases, three had motor developmental delays and one had delayed speech acquisition (Gentile and Fusco, ).…”